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A Phase 2 Open-Label Study of the Efficacy and Safety of ABT-199 (GDC-0199) in Chronic Lymphocytic Leukemia (CLL) Subjects With Relapse or Refractory to B-Cell Receptor Signaling Pathway Inhibitor Therapy

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ClinicalTrials.gov Identifier: NCT02141282
Recruitment Status : Completed
First Posted : May 19, 2014
Results First Posted : December 19, 2022
Last Update Posted : December 19, 2022
Sponsor:
Collaborator:
Roche-Genentech
Information provided by (Responsible Party):
AbbVie

Study Description
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Brief Summary:
This was an open-label, non-randomized, multicenter, Phase 2 study evaluating the efficacy and safety of ABT-199 in 127 participants with relapsed or refractory chronic lymphocytic leukemia (CLL) after B-cell receptor signaling pathway inhibitors (BCR PI) treatment.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Venetoclax Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 127 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Open-Label Study of the Efficacy and Safety of ABT-199 (GDC-0199) in Chronic Lymphocytic Leukemia Subjects With Relapse or Refractory to B-Cell Receptor Signaling Pathway Inhibitor Therapy
Actual Study Start Date : September 10, 2014
Actual Primary Completion Date : December 22, 2021
Actual Study Completion Date : December 22, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Venetoclax

Arms and Interventions
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Arm Intervention/treatment
Experimental: ABT-199 after ibrutinib therapy
Participants with ibrutinib-resistant or refractory chronic lymphocytic leukemia (CLL) received venetoclax tablets once daily (QD) until disease progression or study drug discontinuation; median time on treatment was 593 days. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.
 Drug: Venetoclax
Each dose of venetoclax was to be taken with approximately 240 mL of water within 30 minutes after the completion of breakfast or the participant's first meal of the day.
Other Names:
  • ABT-199
  • VENCLEXTA®
Experimental: ABT-199 after idelalisib therapy
Participants with idelalisib-resistant or refractory chronic lymphocytic leukemia (CLL) received venetoclax tablets once daily (QD) until disease progression or study drug discontinuation; median time on treatment was 1023 days. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg.
 Drug: Venetoclax
Each dose of venetoclax was to be taken with approximately 240 mL of water within 30 minutes after the completion of breakfast or the participant's first meal of the day.
Other Names:
  • ABT-199
  • VENCLEXTA®
Experimental: ABT-199 after ibrutinib therapy: Expansion Cohort
Participants with ibrutinib-resistant or refractory chronic lymphocytic leukemia (CLL) received venetoclax tablets once daily (QD) until disease progression or study drug discontinuation; median time on treatment was 622 days. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg. Participants enrolled into the Expansion Cohort with bulky disease at study entry who were non-responders or those who showed signs of clinical progression after completing the ramp up to 400 mg either by clinical disease assessment or by CT/MRI scan between Week 6 to Week 12 may have been permitted to escalate venetoclax to a daily dose of 600 mg.
 Drug: Venetoclax
Each dose of venetoclax was to be taken with approximately 240 mL of water within 30 minutes after the completion of breakfast or the participant's first meal of the day.
Other Names:
  • ABT-199
  • VENCLEXTA®
Experimental: ABT-199 after idelalisib therapy: Expansion Cohort
Participants with idelalisib-resistant or refractory chronic lymphocytic leukemia (CLL) received venetoclax tablets once daily (QD) until disease progression or study drug discontinuation; median time on treatment was 1189 days. The starting dose was 20 mg daily, increasing over a period of 5 weeks up to the daily dose of 400 mg. Participants enrolled into the Expansion Cohort with bulky disease at study entry who were non-responders or those who showed signs of clinical progression after completing the ramp up to 400 mg either by clinical disease assessment or by CT/MRI scan between Week 6 to Week 12 may have been permitted to escalate venetoclax to a daily dose of 600 mg.
 Drug: Venetoclax
Each dose of venetoclax was to be taken with approximately 240 mL of water within 30 minutes after the completion of breakfast or the participant's first meal of the day.
Other Names:
  • ABT-199
  • VENCLEXTA®


Outcome Measures
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Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort ]
    Overall response rate is defined as the percentage of participants with an overall response (per the investigator assessment) 2008 Modified International Workshop for Chronic Lymphocytic Leukemia (IWCLL) National Cancer Institute-Working Group (NCI-WG) criteria.


Secondary Outcome Measures :
  1. Duration of Response (DOR) [ Time Frame: At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort ]
    DOR is defined as the number of days from the date of first response (complete response [CR], complete response with incomplete marrow recovery [CRi], nodular partial remission [nPR], or partial remission [PR]) to the earliest recurrence or progressive disease. DOR was analyzed by Kaplan-Meier (K-M) methodology.

  2. Time to Progression (TTP) [ Time Frame: At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort ]

    TTP is defined as the number of days from the date of first dose to the date of earliest disease progression (PD).

    TTP was analyzed by Kaplan-Meier (K-M) methodology.


  3. Progression-free Survival (PFS) [ Time Frame: At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort ]
    PFS is defined as the number of days from the date of first dose to the date of earliest disease progression (PD) or death. PFS was analyzed by Kaplan-Meier methodology.

  4. Overall Survival (OS) [ Time Frame: At Wk 5, Day 1; Wk 8, Day 1; Wk 12, Day 1; Wk 16, Day 1; Wk 20, Day 1; Wk 24, Day 1; Wk 36, Day 1; every 12 wks after Wk 36; Final Visit; estimated median time on follow-up was 1694 d for ibrutinib failure cohort and 1942 d for idelalisib failure cohort ]
    OS is defined as the number of days from the date of first dose to the date of death for all dosed participants. For participants who did not die, their data was censored at the date of last study visit or the last known date to be alive, whichever was later. OS was estimated using Kaplan-Meier methodology.


Other Outcome Measures:
  1. Time to Next Anti-Chronic Lymphocytic Leukemia Treatment (TNNT) [ Time Frame: Collected every 3 months for a period of 5 years after the last participant had enrolled into the study ]
    TNNT is defined as the number of days from the date of the first dose of venetoclax to the date of first dose of any non-protocol anti-leukemia therapy (NPT) or death from any cause. For participants who did not take NPT, their data was censored at the last known date to be free of NPT. TTNT was analyzed by Kaplan-Meier methodology.

  2. Percentage of Participants With Minimal Residual Disease (MRD) Negativity Status [ Time Frame: Assessed at Week 24, Day 1; after the first Complete Response, Complete Remission with Incomplete Marrow Recovery, or Partial Response; at 12-week interval visits until two consecutive negative MRD levels were reported ]
    The rate of MRD response is defined as the percentage of participants who had MRD negative status.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant must have a diagnosis of chronic lymphocytic leukemia (CLL) that meets 2008 Modified International Workshop on Chronic Lymphocytic Leukemia National Cancer Institute-Working Group (IWCLL NCI-WG) criteria
  • Participant has relapsed/refractory disease with an indication for treatment
  • Participant has refractory disease or developed recurrence after therapy with a B-cell receptor pathway inhibitor (BCR PI)
  • Participant must have an Eastern Cooperative Oncology Group performance score of ≤ 2
  • Participant must have adequate bone marrow function at Screening
  • Participant must have adequate coagulation profile, renal, and hepatic function, per laboratory reference range at Screening

Exclusion Criteria:

  • Participant has undergone an allogeneic stem cell transplant within the past year
  • Participant has developed Richter's transformation confirmed by biopsy
  • Participant has active and uncontrolled autoimmune cytopenia
  • Participant has malabsorption syndrome or other condition that precludes enteral route of administration
  • Participant is human immunodeficiency virus (HIV) positive or has chronic hepatitis B or hepatitis C virus requiring treatment
  • Participant has known contraindication or allergy to both xanthine oxidase inhibitors and rasburicase
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02141282


Locations
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United States, California
Moores Cancer Center at UC San Diego /ID# 128535
La Jolla, California, United States, 92093
University of California, Los Angeles /ID# 127262
Los Angeles, California, United States, 90095
Stanford University School of Med /ID# 126495
Stanford, California, United States, 94305-2200
United States, District of Columbia
Georgetown University Hospital /ID# 127261
Washington, District of Columbia, United States, 20007
United States, Georgia
Emory Midtown Infectious Disease Clinic /ID# 131249
Atlanta, Georgia, United States, 30322
United States, Illinois
Northwestern University Feinberg School of Medicine /ID# 126497
Chicago, Illinois, United States, 60611-2927
United States, Massachusetts
Beth Israel Deaconess Medical Center /ID# 134509
Boston, Massachusetts, United States, 02215-5400
Dana-Farber Cancer Institute /ID# 126496
Boston, Massachusetts, United States, 02215
United States, New York
Columbia Univ Medical Center /ID# 128536
New York, New York, United States, 10032-3725
New York Presbyterian Hospital Weill Cornell Medical Center /ID# 129648
New York, New York, United States, 10032-3725
Univ Rochester Med Ctr /ID# 130011
Rochester, New York, United States, 14642
United States, Ohio
The Ohio State University /ID# 127263
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pennsylvania /ID# 126860
Philadelphia, Pennsylvania, United States, 19104-5502
United States, Texas
University of Texas MD Anderson Cancer Center /ID# 126498
Houston, Texas, United States, 77030
United States, Utah
University of Utah /ID# 130813
Salt Lake City, Utah, United States, 84112-5500
Sponsors and Collaborators
AbbVie
Roche-Genentech
Investigators
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Study Director: ABBVIE INC. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Study Protocol  [PDF] December 15, 2020
Statistical Analysis Plan  [PDF] November 9, 2018

More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02141282    
Other Study ID Numbers: M14-032
First Posted: May 19, 2014    Key Record Dates
Results First Posted: December 19, 2022
Last Update Posted: December 19, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
URL: https://vivli.org/ourmember/abbvie/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
Oncology
Chronic Lymphocytic Leukemia
Cancer of the blood and bone marrow
Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Chronic Disease
Disease Attributes
Pathologic Processes
Venetoclax
Antineoplastic Agents